Pyrimethamine hematologic toxicity

Pyrimethamine: Hematologic Toxicity

Pyrimethamine (Daraprim) is an antifolate drug that has been used to treat toxoplasmosis, malaria, and other infectious diseases for decades. Despite its utility, pyrimethamine carries a significant risk of hematologic toxicity, which may lead to serious side effects. Therefore, it is important to understand the mechanisms underlying this potential toxicity in order to ensure patient safety and to identify methods for preventing and managing this condition.

Hematologic toxicity is a serious reaction associated with the use of pyrimethamine and is characterized by two primary side effects: myelosuppression— including anemia, thrombocytopenia, and neutropenia—and macrocytic anemia. Myelosuppression occurs due to the drug’s effect on DNA synthesis, which leads to a decrease in the production of red and white blood cells as well as platelets. Macrocytic anemia occurs when the drug reduces folate levels, leading to a decrease in hemoglobin production.

A variety of additional adverse effects are known to be associated with pyrimethamine, including gastrointestinal symptoms such as nausea, vomiting, and diarrhea, as well as rash, fever, and headache. More serious side effects, including Stevens-Johnson syndrome, can occur in rare cases. These side effects are more likely to occur when pyrimethamine is taken in combination with other drugs or when dosages are exceeded

Preventing and Treating Hematologic Toxicity

Since hematologic toxicity is a serious side effect of pyrimethamine, it is important to take measures to reduce the risk of this condition. First, patients should be closely monitored during therapy to identify any changes in blood count that may indicate a decrease in red or white blood cells or platelets. Additionally, patients should be instructed on appropriate dosing and the potential for serious side effects.

If hematologic toxicity does occur, treatment will depend on severity and may include adjusting the dose of pyrimethamine, supplementing with folate, or switching to an alternative drug. In some cases, supportive care may also be necessary, such as transfusions of red blood cells or platelets. In all instances, close monitoring is necessary as any changes in blood count need to be identified and addressed quickly to prevent any potential complications.


Pyrimethamine is a useful antifolate drug that has been used to treat a variety of different infectious diseases. However, it is also associated with a significant risk of hematologic toxicity, including myelosuppression, macrocytic anemia, and a variety of other side effects. Therefore, it is important to understand both the mechanisms of this potential toxicity as well as methods for preventing and treating it.